Long duration spaceflight crews have relied heavily on virtually constant communication with ground control mission support. Ground control teams provide vehicle status and system monitoring, while offering near real-time support for nominal tasks, emergencies, and general well-being of the crew. For the lunar and Mars outposts, real-time communication with ground control teams and the ground's ability to conduct mission monitoring will be limited, compared to the resources provided to current International Space Station (ISS) crews. NASA's future exploration endeavors and increased autonomy, crew self governance, needs will require an operational shift toward more autonomy and heavier reliance on the crew to monitor their vehicle and operations. This will include changes in crew skill composition, i.e. engineer, doctor, mission specialist etc., and will lead to new training challenges and mission scenarios. New operational and design challenges are evident in many areas including: Habitat Infrastructure and Support Systems, Crew Composition, Training, Procedures, Mission Planning and Communication. This paper will address how NASA can utilize the ISS to evaluate and understand how to conduct fully autonomous operations successfully. The ISS is a critical component for evaluating this operational approach. The ISS creates an opportunity to gather long duration lessons learned specific to autonomy, which do not currently exist for long duration space flight. Understanding these lessons learned and applying them to future operations will help to reduce costly impacts associated with issues related to increased levels of crew autonomy.